Infectious disease (ID), antimicrobial stewardship (ASP), and the inextricable link with public health have become increasingly important areas of study and practice in recent decades due to shifting disease patterns, the emergence of new infectious pathogens, and the adoption of a One Health approach. As defined by the World Health Organization, a One Health approach is intended to be a comprehensive and unifying perspective to balance and optimize human, domestic and wild animals, plants, and the wider environment when considering the impact on an ecosystem.1 Pharmacists play a crucial role in ASP and ID teams, positively impacting antimicrobial use and therefore the One Health approach.2–5
Our clinical, didactic, and experience-based education programs prepare learners for the myriad of experiences and opportunities that can be obtained within the space of ID; however, the breadth and depth of knowledge obtained from published studies as a new practicing clinician can be overwhelming due to the quantity of evidence that becomes available on a daily basis. Resources such as the Society of Infectious Diseases Pharmacists (SIDP)’s “Breakpoints.” and the “Infectious Disease Puscast,” as well as other tertiary references offer timely updates on important clinical topics. Therefore, in the spirit of supporting learners in the ID space, we present our top five recommended topics with resources that every ID learner should explore.
Busting Some Myths
Some of our recommended readings challenge common misconceptions and highlight evolving practices in antimicrobial use. A recent publication summarizes some of the commonly held myths in the ID world.6 Rather than going into detail on each topic here, we suggest that you review the table below and use the references in the table as well as the article by McCreary et al, for further reading.
Place in Therapy for Oral Antibiotics
Over the last decade, there has been a notable shift towards the use of oral therapies in complex infections ranging from bacteremias to endocarditis, and osteomyelitis. A systematic review conducted by Wald-Dickler et al. summarizes recent evidence supporting the use of oral (PO) therapies where intravenous (IV) was generally considered the gold standard.27 Below we summarize two landmark studies that were discussed in the review but in total, the authors describe 21 studies. We would recommend reading through the entire paper. The authors also conducted meta-analyses of studies for the treatment of osteomyelitis, bacteremia, and endocarditis. For osteomyelitis and bacteremia, the meta-analyses showed no statistical difference between PO and IV for treatment success. For endocarditis, PO was more likely to result in statistically significant treatment success than IV in a meta-analysis of four studies. It is important that clinicians consider the different facets of the described studies, such as IV lead-in periods and inclusion criteria when determining generalizability and transportability to their respective populations.
Is Shorter Better and When?
Antibiotic durations are easy to remember if you can remember that there are 5 fingers on each hand, and 7 days in every week.
“In AD 321, Roman Emperor Constantine the Great codified that there would be 7 days in a week. …this [1700]-year-old decree remains a primary reference for duration of antibiotic therapy: it leads physicians to treat infections in intervals of 7 days.”30
Determining the optimal duration for treatment of an infection can be challenging. Historically longer treatment durations were believed to prevent antibiotic resistance; however, the opposite is likely true. Prolonged antibiotics can lead to resistance in commensal bacteria. The rationale behind shorter courses of antibiotics is three-fold. Firstly, by reducing the time patients are on antibiotics, we lessen the likelihood of adverse outcomes, such as Clostridioides difficile. Secondly, shorter durations result in lower overall exposure of commensal organisms to the antibiotic, therefore lowering the likelihood of resistance developing. Lastly, shorter durations decrease healthcare costs. The table below, based on commentary by Spellberg and Rice, provides examples of treatment durations for common infections, and the exceptions where shorter is not better. 31 Keep in mind, of course, that not all infections are bacterial and thus do not require any antibiotics (eg bronchitis). Also note that the table below is not all inclusive; rather, it is a summary of commonly seen infections in the acute care setting. For further resources, we suggest reviewing Brad Spellberg's, MD, website.
Bacteriostatic or Bactericidal?
When antibiotic therapies are newly discovered, a component of determining efficacy in vitro is assessing the agent’s ability to both inhibit bacterial growth and to kill the bacteria of interest.48 However, the clinical application of these in-vitro standards tends to be less clear. Two notable publications on this topic are by Pankey and Sabbath in 200448 and Wald-Dickler et al, in 2018.49 We will highlight select studies from Wald-Dickler et al, and suggest that readers review the supplementary material that lists prospective RCTs comparing bacteriostatic and bactericidal agents. However, both publications offer engaging insights into the "static" versus "cidal" debate.
Penicillin Allergies: Oral Challenge and A Risk Stratification Algorithm
Another important area for ASP consideration that impacts both the safety and efficacy of antimicrobial use is the presence of penicillin allergy labels. Approximately 10% of the general population carries the label of penicillin allergy on their electronic medical record, with a prevalence closer to 15% for hospitalized individuals.53,54 The presence of penicillin allergy labels is associated with prolonged length of stay,55 increased adverse effects and worse clinical outcomes,56 higher rates of surgical site infections,57 and an increased risk of multidrug-resistant organisms.58 About 90% of penicillin allergies can be safely delabeled using various approaches such as penicillin skin testing (PST) or oral challenge (OC).59-61 Below are 2 studies that describe both risk stratification of penicillin allergies in surgical patients, and the use of oral challenge in low-risk individuals. These studies are selected since PST is often difficult to conduct in a time-constrained setting and can result in over-labeling in patients with low risk allergies (such as remote non-severe rash or gastrointestinal symptoms) due to low sensitivity. 62,63 This can be a significant limitation given that low-risk penicillin allergies make up about 40% to 50% of the population with a penicillin allergy label. 59,64
We hope that this resource gives learners the opportunity to explore some cutting-edge research in ID and ASP that every ID learner should read about, at least once. This should serve as a starting point for finding primary literature on the topics discussed so learners can dig into more details, consider the evidence, and continue to contribute to the One Health approach through optimizing antimicrobial use.
References
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3.Bohn BC, Neuner EA, Athans V, Rivard KR, Riffle AR, Richter SS, et al. The Implementation and Effect of Weekend Pharmacy-Driven Antimicrobial Stewardship Services at a Large Academic Medical Center. J Pharm Pract. 2022 Aug;35(4):541–5.
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29.Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425–36.
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